The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders
Received date: 02 Jul 2020
Accepted date: 19 Nov 2020
Published date: 15 Jan 2022
Copyright
The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.
Kaifan Zhang , Yan Wang , Tianda Fan , Cheng Zeng , Zhong Sheng Sun . The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders[J]. Protein & Cell, 2022 , 13(1) : 6 -25 . DOI: 10.1007/s13238-020-00812-9
1 |
Allen KM, Gleeson JG, Bagrodia S, Partington MW, MacMillan JC, Cerione RA, Mulley JC, Walsh CA (1998) PAK3 mutation in nonsyndromic X-linked mental retardation. Nat Genet 20:25–30
|
2 |
Arber S, Barbayannis FA, Hanser H, Schneider C, Stanyon CA, Bernard O, Caroni P (1998) Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 393:805–809
|
3 |
Arias-Romero LE, Chernoff J (2008) A tale of two Paks. Biol Cell 100:97–108
|
4 |
Arsenault D, Dal-Pan A, Tremblay C, Bennett DA, Guitton MJ, De Koninck Y, Tonegawa S, Calon F (2013) PAK inactivation impairs social recognition in 3xTg-AD Mice without increasing brain deposition of tau and Abeta. J Neurosci 33:10729–10740
|
5 |
Asrar S, Meng Y, Zhou Z, Todorovski Z, Huang WW, Jia Z (2009) Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1). Neuropharmacology 56:73–80
|
6 |
Aston C, Jiang L, Sokolov BP (2005) Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry. 10:309–322
|
7 |
Banko MR, Allen JJ, Schaffer BE, Wilker EW, Tsou P, White JL, Villén J, Wang B, Kim SR, Sakamoto K
|
8 |
Barton B, North K (2004) Social skills of children with neurofibromatosis type 1. Dev Med Child Neurol 46:553–563
|
9 |
Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E (2012) Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 76:325–337
|
10 |
Bienvenu T, des Portes V, McDonell N, Carrié A, Zemni R, Couvert P, Ropers HH, Moraine C, van Bokhoven H, Fryns JP
|
11 |
Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, Kajiwara Y, Yang M, Katz AM, Scattoni ML
|
12 |
Brown MD, Cornejo BJ, Kuhn TB, Bamburg JR (2000) Cdc42 stimulates neurite outgrowth and formation of growth cone filopodia and lamellipodia. J Neurobiol 43:352–364
|
13 |
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857–868
|
14 |
Byrne KM, Monsefi N, Dawson JC, Degasperi A, Bukowski-Wills JC, Volinsky N, Dobrzynski M, Birtwistle MR, Tsyganov MA, Kiyatkin A
|
15 |
Causeret F, Terao M, Jacobs T, Nishimura YV, Yanagawa Y, Obata K, Hoshino M, Nikolic M (2009) The p21-activated kinase is required for neuronal migration in the cerebral cortex. Cereb Cortex 19:861–875
|
16 |
Chen LY, Rex CS, Babayan AH, Kramár EA, Lynch G, Gall CM, Lauterborn JC (2010) Physiological activation of synaptic Rac>PAK (p-21 activated kinase) signaling is defective in a mouse model of fragile X syndrome. J Neurosci 30:10977–10984
|
17 |
Chen Q, Chen TJ, Letourneau PC, Costa Lda F, Schubert D (2005) Modifier of cell adhesion regulates N-cadherin-mediated cell-cell adhesion and neurite outgrowth. J Neurosci 25:281–290
|
18 |
Chen Q, Peto CA, Shelton GD, Mizisin A, Sawchenko PE, Schubert D (2009) Loss of modifier of cell adhesion reveals a pathway leading to axonal degeneration. J Neurosci 29:118–130
|
19 |
Chen SY, Huang PH, Cheng HJ (2011) Disrupted-in-Schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling. Proc Natl Acad Sci U S A. 108:5861–5866
|
20 |
Chenette EJ, Mitin NY, Der CJ (2006) Multiple sequence elements facilitate Chp Rho GTPase subcellular location, membrane association, and transforming activity. Mol Biol Cell 17:3108–3121
|
21 |
Civiero L, Cirnaru MD, Beilina A, Rodella U, Russo I, Belluzzi E, Lobbestael E, Reyniers L, Hondhamuni G, Lewis PA
|
22 |
Cobos I, Borello U, Rubenstein JL (2007) Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron 54:873–888
|
23 |
Cooper JA (2013) Cell biology in neuroscience: mechanisms of cell migration in the nervous system. J Cell Biol 202:725–734
|
24 |
Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ (2002) Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415:526–530
|
25 |
Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ (2008) Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 135:549–560
|
26 |
Dai X, Iwasaki H, Watanabe M, Okabe S (2014) Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression. Eur J Neurosci 39:531–547
|
27 |
Daniels RH, Bokoch GM (1999) p21-activated protein kinase: a crucial component of morphological signaling? Trends Biochem Sci 24:350–355
|
28 |
Darnell JC, Klann E (2013) The translation of translational control by FMRP: therapeutic targets for FXS. Nat Neurosci 16:1530–1536
|
29 |
Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, Stone EF, Chen C, Fak JJ, Chi SW
|
30 |
Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909
|
31 |
de la Torre-Ubieta L, Gaudilliere B, Yang Y, Ikeuchi Y, Yamada T, DiBacco S, Stegmuller J, Schuller U, Salih DA, Rowitch D
|
32 |
de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH (2016) Advancing the understanding of autism disease mechanisms through genetics. Nat Med 22:345–361
|
33 |
Dolan BM, Duron SG, Campbell DA, Vollrath B, Shankaranarayana Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A. 110:5671–5676
|
34 |
Dong X, Liao Z, Gritsch D, Hadzhiev Y (2018) Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nat Neurosci 21:1482–1492
|
35 |
Duarte K, Heide S, Poea-Guyon S, Rousseau V, Depienne C, Rastetter A, Nava C, Attie-Bitach T, Razavi F, Martinovic J
|
36 |
Dubos A, Combeau G, Bernardinelli Y, Barnier JV, Hartley O, Gaertner H, Boda B, Muller D (2012) Alteration of synaptic network dynamics by the intellectual disability protein PAK3. J Neurosci 32:519–527
|
37 |
Duffney LJ, Wei J, Cheng J, Liu W, Smith KR, Kittler JT, Yan Z (2013) Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism. J Neurosci 33:15767–15778
|
38 |
Eswaran J, Soundararajan M, Kumar R, Knapp S (2008) UnPAKing the class differences among p21-activated kinases. Trends Biochem Sci 33:394–403
|
39 |
Feng J, Chen S, Wang Y, Liu Q, Yang M, Li X, Nie C, Qin J, Chen H, Yuan X
|
40 |
Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E, Palta P, Ruderfer DM
|
41 |
Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792–1795
|
42 |
Gao J, Ha BH, Lou HJ, Morse EM, Zhang R, Calderwood DA, Turk BE, Boggon TJ (2013) Substrate and inhibitor specificity of the type II p21-activated kinase, PAK6. PLoS ONE 8:e77818
|
43 |
Garg S, Green J, Leadbitter K, Emsley R, Lehtonen A, Evans DG, Huson SM (2013) Neurofibromatosis type 1 and autism spectrum disorder. Pediatrics 132:e1642–e1648
|
44 |
Gedeon AK, Nelson J, Gécz J, Mulley JC (2003) X-linked mild nonsyndromic mental retardation with neuropsychiatric problems and the missense mutation A365E in PAK3. Am J Med Genet A 120a:509–517
|
45 |
Glantz LA, Lewis DA (2001) Dendritic spine density in schizophrenia and depression. Arch Gen Psychiatry 58:203
|
46 |
Gottle P, Sabo JK, Heinen A, Venables G, Torres K (2015) Oligodendroglial maturation is dependent on intracellular protein shuttling. J Neurosci 35:906–919
|
47 |
Gotz M, Barde YA (2005) Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons. Neuron 46:369–372
|
48 |
Gu Z, Cheng J, Zhong P, Qin L, Liu W, Yan Z (2014) Abeta selectively impairs mGluR7 modulation of NMDA signaling in basal forebrain cholinergic neurons: implication in Alzheimer’s disease. J Neurosci 34:13614–13628
|
49 |
Guo D, Tan YC, Wang D, Madhusoodanan KS, Zheng Y, Maack T, Zhang JJ, Huang XY (2007) A Rac-cGMP signaling pathway. Cell. 128:341–355
|
50 |
Ha BH, Boggon TJ (2018) CDC42 binds PAK4 via an extended GTPase-effector interface. Proc Natl Acad Sci U S A. 115:531–536
|
51 |
Ha BH, Davis MJ, Chen C, Lou HJ, Gao J, Zhang R, Krauthammer M, Halaban R, Schlessinger J, Turk BE
|
52 |
Harms FL, Kloth K, Bley A, Denecke J, Santer R, Lessel D, Hempel M, Kutsche K (2018) Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a Neurodevelopmental Disorder. Am J Hum Genet 103:579–591
|
53 |
Hayashi-Takagi A, Araki Y, Nakamura M, Vollrath B, Duron SG, Yan Z, Kasai H, Huganir RL, Campbell DA, Sawa A (2014) PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. Proc Natl Acad Sci U S A. 111:6461–6466
|
54 |
Hayashi ML, Choi SY, Rao BS, Jung HY, Lee HK, Zhang D, Chattarji S, Kirkwood A, Tonegawa S (2004) Altered cortical synaptic morphology and impaired memory consolidation in forebrainspecific dominant-negative PAK transgenic mice. Neuron 42:773–787
|
55 |
Hayashi ML, Rao BS, Seo JS, Choi HS, Dolan BM, Choi SY, Chattarji S, Tonegawa S (2007) Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A. 104:11489–11494
|
56 |
Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11:1975–1980
|
57 |
Hing H, Xiao J, Harden N, Lim L, Zipursky SL (1999) Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Cell 97:853–863
|
58 |
Hoekman MF, Jacobs FM, Smidt MP, Burbach JP (2006) Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr Patterns 6:134–140
|
59 |
Horn S, Au M, Basel-Salmon L, Bayrak-Toydemir P, Chapin A, Cohen L, Elting MW, Graham JM, Gonzaga-Jauregui C, Konen O
|
60 |
Hu B, Arpag S, Zhang X, Möbius W, Werner H, Sosinsky G, Ellisman M, Zhang Y, Hamilton A, Chernoff J
|
61 |
Huang W, Zhou Z, Asrar S, Henkelman M, Xie W, Jia Z (2011) p21Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties. Mol Cell Biol 31:388–403
|
62 |
Huijbregts S, Jahja R, De Sonneville L, de Breij S, Swaab-Barneveld H (2010) Social information processing in children and adolescents with neurofibromatosis type 1. Dev Med Child Neurol 52:620–625
|
63 |
Huijbregts SC, de Sonneville LM (2011) Does cognitive impairment explain behavioral and social problems of children with neurofibromatosis type 1? Behav Genet 41:430–436
|
64 |
Hussain NK, Thomas GM, Luo J, Huganir RL (2015) Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation. Proc Natl Acad Sci U S A. 112:E5883–E5890
|
65 |
Jacobs T, Causeret F, Nishimura YV, Terao M, Norman A, Hoshino M, Nikolic M (2007) Localized activation of p21-activated kinase controls neuronal polarity and morphology. J Neurosci 27:8604–8615
|
66 |
Jaffer ZM, Chernoff J (2002) p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol 34:713–717
|
67 |
Jan YN, Jan LY (2003) The control of dendrite development. Neuron 40:229–242
|
68 |
Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanović D, Geschwind DH, Mane SM, State MW, Sestan N (2009) Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62:494–509
|
69 |
Kamiya A, Kubo K, Tomoda T, Takaki M, Youn R, Ozeki Y, Sawamura N, Park U, Kudo C, Okawa M
|
70 |
Kamiyama D, McGorty R, Kamiyama R, Kim MD, Chiba A, Huang B (2015) Specification of Dendritogenesis Site in Drosophila aCC Motoneuron by Membrane Enrichment of Pak1 through Dscam1. Dev Cell 35:93–106
|
71 |
Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G
|
72 |
Kennedy LM, Pham SC, Grishok A (2013) Nonautonomous regulation of neuronal migration by insulin signaling, DAF-16/FOXO, and PAK-1. Cell Rep. 4:996–1009
|
73 |
Kim MJ, Biag J, Fass DM, Lewis MC, Zhang Q, Fleishman M, Gangwar SP, Machius M, Fromer M, Purcell SM
|
74 |
Knaus UG, Bokoch GM (1998) The p21Rac/Cdc42-activated kinases (PAKs). Int J Biochem Cell Biol 30:857–862
|
75 |
Kong D, Dagon Y, Campbell JN, Guo Y, Yang Z, Yi X, Aryal P, Wellenstein K, Kahn BB, Sabatini BL
|
76 |
Kreis P, Barnier JV (2009) PAK signalling in neuronal physiology. Cell Signal 21:384–393
|
77 |
Kuijl C, Savage ND, Marsman M, Tuin AW, Janssen L, Egan DA, Ketema M, van den Nieuwendijk R, van den Eeden SJ, Geluk A
|
78 |
Lamoureux P, Altun-Gultekin ZF, Lin C, Wagner JA, Heidemann SR (1997) Rac is required for growth cone function but not neurite assembly. J Cell Sci 110(Pt 5):635–641
|
79 |
Lauterborn JC, Cox CD, Chan SW, Vanderklish PW, Lynch G, Gall CM (2020) Synaptic actin stabilization protein loss in Down syndrome and Alzheimer disease. Brain Pathol 30:319–331
|
80 |
Lee RY, Hench J, Ruvkun G (2001) Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 11:1950–1957
|
81 |
Lehtonen A, Howie E, Trump D, Huson SM (2013) Behaviour in children with neurofibromatosis type 1: cognition, executive function, attention, emotion, and social competence. Dev Med Child Neurol 55:111–125
|
82 |
Lei M, Lu W, Meng W, Parrini MC, Eck MJ, Mayer BJ, Harrison SC (2000) Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell 102:387–397
|
83 |
Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ
|
84 |
Leung C, Cao F, Nguyen R, Joshi K, Aqrabawi AJ, Xia S, Cortez MA, Snead OC 3rd, Kim JC, Jia Z (2018) Activation of Entorhinal Cortical Projections to the Dentate Gyrus Underlies Social Memory Retrieval. Cell Rep. 23:2379–2391
|
85 |
Lewis DA, Glantz LA, Pierri JN, Sweet RA (2003) Altered cortical glutamate neurotransmission in schizophrenia: evidence from morphological studies of pyramidal neurons. Ann N Y Acad Sci 1003:102–112
|
86 |
Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409–432
|
87 |
Li S, Leshchyns’ka I, Chernyshova Y, Schachner M, Sytnyk V (2013) The neural cell adhesion molecule (NCAM) associates with and signals through p21-activated kinase 1 (Pak1). J Neurosci 33:790–803
|
88 |
Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF1 and germline signaling. Nat Genet 28:139–145
|
89 |
Liu J, Liu Y, Shao J, Li Y, Qin L, Shen H, Xie Y, Xia W (2019) Zeb1 is important for proper cleavage plane orientation of dividing progenitors and neuronal migration in the mouse neocortex. Cell Death Differ 26:2479–2492
|
90 |
Lucanic M, Kiley M, Ashcroft N, L’Etoile N, Cheng HJ (2006) The Caenorhabditis elegans P21-activated kinases are differentially required for UNC-6/netrin-mediated commissural motor axon guidance. Development. 133:4549–4559
|
91 |
Ma QL, Yang F, Calon F, Ubeda OJ, Hansen JE, Weisbart RH, Beech W, Frautschy SA, Cole GM (2008) p21-activated kinaseaberrant activation and translocation in Alzheimer disease pathogenesis. J Biol Chem 283:14132–14143
|
92 |
Maglorius Renkilaraj MRL, Baudouin L, Wells CM, Doulazmi M, Wehrle R, Cannaya V, Bachelin C, Barnier JV, Jia Z, Nait Oumesmar B
|
93 |
Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L (1994) A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367:40–46
|
94 |
Marin O, Valiente M, Ge X, Tsai LH (2010) Guiding neuronal cell migrations. Cold Spring Harb Perspect Biol. 2:a001834
|
95 |
Martini FJ, Valiente M, Lopez Bendito G, Szabo G, Moya F, Valdeolmillos M, Marin O (2009) Biased selection of leading process branches mediates chemotaxis during tangential neuronal migration. Development. 136:41–50
|
96 |
Meng J, Meng Y, Hanna A, Janus C, Jia Z (2005) Abnormal longlasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3. J Neurosci 25:6641–6650
|
97 |
Molosh AI, Johnson PL, Spence JP, Arendt D, Federici LM, Bernabe C, Janasik SP, Segu ZM, Khanna R, Goswami C
|
98 |
Murata Y, Constantine-Paton M (2013) Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway. J Neurosci 33:5040–5052
|
99 |
Nakai Y, Zheng Y, MacCollin M, Ratner N (2006) Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. J Neurosci 26:3390–3395
|
100 |
Nekrasova T, Jobes ML, Ting JH, Wagner GC, Minden A (2008) Targeted disruption of the Pak5 and Pak6 genes in mice leads to deficits in learning and locomotion. Dev Biol 322:95–108
|
101 |
Nguyen TV, Galvan V, Huang W, Banwait S, Tang H, Zhang J, Bredesen DE (2008) Signal transduction in Alzheimer disease: p21-activated kinase signaling requires C-terminal cleavage of APP at Asp664. J Neurochem 104:1065–1080
|
102 |
Nikolic M, Chou MM, Lu W, Mayer BJ, Tsai LH (1998) The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity. Nature 395:194–198
|
103 |
Nobes CD, Hall A (1995) Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81:53–62
|
104 |
Nobes CD, Hall A (1999) Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol 144:1235–1244
|
105 |
Noll RB, Reiter-Purtill J, Moore BD, Schorry EK, Lovel AM, Vannatta K, Gerhardt CA (2007) Social, emotional, and behavioral functioning of children with NF1. Am J Med Genet A 143a:2261–2273
|
106 |
O’Donnell M, Chance RK, Bashaw GJ (2009) Axon growth and guidance: receptor regulation and signal transduction. Annu Rev Neurosci 32:383–412
|
107 |
O’Donnell WT, Warren ST (2002) A decade of molecular studies of fragile X syndrome. Annu Rev Neurosci 25:315–338
|
108 |
Parrini MC, Camonis J, Matsuda M, de Gunzburg J (2009) Dissecting activation of the PAK1 kinase at protrusions in living cells. J Biol Chem 284:24133–24143
|
109 |
Parrini MC, Lei M, Harrison SC, Mayer BJ (2002) Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell 9:73–83
|
110 |
Peca J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, Lascola CD, Fu Z, Feng G (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:437–442
|
111 |
Peippo M, Koivisto AM, Särkämö T, Sipponen M, von Koskull H, Ylisaukko-oja T, Rehnström K, Froyen G, Ignatius J, Järvelä I (2007) PAK3 related mental disability: further characterization of the phenotype. Am J Med Genet A 143a:2406–2416
|
112 |
Pensold D, Symmank J, Hahn A, Lingner T, Salinas-Riester G, Downie BR, Ludewig F, Rotzsch A, Haag N, Andreas N
|
113 |
Penzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, Huganir RL (2003) Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37:263–274
|
114 |
Pereanu W, Larsen EC, Das I, Estevez MA, Sarkar AA, SpringPearson S, Kollu R, Basu SN, Banerjee-Basu S (2018) AutDB: a platform to decode the genetic architecture of autism. Nucleic Acids Res 46:D1049–D1054
|
115 |
Pirruccello M, Sondermann H, Pelton JG, Pellicena P, Hoelz A, Chernoff J, Wemmer DE, Kuriyan J (2006) A dimeric kinase assembly underlying autophosphorylation in the p21 activated kinases. J Mol Biol 361:312–326
|
116 |
Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N (2014) Temporal specification and bilaterality of human neocortical topographic gene expression. Neuron 81:321–332
|
117 |
Pride NA, Korgaonkar MS, Barton B, Payne JM, Vucic S, North KN (2014) The genetic and neuroanatomical basis of social dysfunction: lessons from neurofibromatosis type 1. Hum Brain Mapp 35:2372–2382
|
118 |
Purcell SM, Moran JL, Fromer M, Ruderfer D, Solovieff N, Roussos P, O’Dushlaine C, Chambert K, Bergen SE, Kahler A
|
119 |
Pyronneau A, He Q, Hwang JY (2017) Aberrant Rac1-cofilin signaling mediates defects in dendritic spines, synaptic function, and sensory perception in fragile X syndrome. Sci Signal 10eaan0852
|
120 |
Qu J, Li X, Novitch BG, Zheng Y, Kohn M, Xie JM, Kozinn S, Bronson R, Beg AA, Minden A (2003) PAK4 kinase is essential for embryonic viability and for proper neuronal development. Mol Cell Biol 23:7122–7133
|
121 |
Quintero-Rivera F, Sharifi-Hannauer P, Martinez-Agosto JA (2010) Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: case report and review. Am J Med Genet A 152a:2459–2467
|
122 |
Radu M, Semenova G, Kosoff R, Chernoff J (2014) PAK signalling during the development and progression of cancer. Nat Rev Cancer 14:13–25
|
123 |
Ramos CI, Igiesuorobo O, Wang Q, Serpe M (2015) Neto-mediated intracellular interactions shape postsynaptic composition at the Drosophila neuromuscular junction. PLoS Genet 11:e1005191
|
124 |
Rane CK, Minden A (2014) P21 activated kinases: structure, regulation, and functions. Small GTPases. 5:1–11
|
125 |
Rashid T, Banerjee M, Nikolic M (2001) Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology. J Biol Chem 276:49043–49052
|
126 |
Rejeb I, Saillour Y, Castelnau L, Julien C, Bienvenu T, Taga P, Chaabouni H, Chelly J, Ben Jemaa L, Bahi-Buisson N (2008) A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features. Eur J Hum Genet 16:1358–1363
|
127 |
Richier L, Williton K, Clattenburg L, Colwill K, O’Brien M, Tsang C, Kolar A, Zinck N, Metalnikov P, Trimble WS
|
128 |
Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52:139–153
|
129 |
Rubio MD, Haroutunian V, Meador-Woodruff JH (2012) Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21activated kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in schizophrenia. Biol Psychiatry 71:906–914
|
130 |
Sanders LC, Matsumura F, Bokoch GM, de Lanerolle P (1999) Inhibition of myosin light chain kinase by p21-activated kinase. Science 283:2083–2085
|
131 |
Santini E, Huynh TN, Longo F, Koo SY, Mojica E, Anderson MJ, Bagni C, Klann E (2017) Reducing eIF4E-eIF4G interactions restores the balance between protein synthesis and actin dynamics in fragile X syndrome model mice. Science Signaling 10:eaan0665
|
132 |
Sells MA, Chernoff J (1997) Emerging from the Pak: the p21activated protein kinase family. Trends Cell Biol 7:162–167
|
133 |
Sivanesan S, Tan A, Rajadas J (2013) Pathogenesis of Abeta oligomers in synaptic failure. Curr Alzheimer Res 10:316–323
|
134 |
Smith KR, Davenport EC, Wei J, Li X, Pathania M, Vaccaro V, Yan Z, Kittler JT (2014) GIT1 and βPIX are essential for GABA (A) receptor synaptic stability and inhibitory neurotransmission. Cell Rep. 9:298–310
|
135 |
Souopgui J, Solter M, Pieler T (2002) XPak3 promotes cell cycle withdrawal during primary neurogenesis in Xenopus laevis. EMBO J 21:6429–6439
|
136 |
Strochlic TI, Concilio S, Viaud J, Eberwine RA, Wong LE, Minden A, Turk BE, Plomann M, Peterson JR (2012) Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking. Proc Natl Acad Sci U S A. 109:4116–4121
|
137 |
Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 60:1187–1192
|
138 |
Tabanifar B, Zhao Z, Manser E (2016) PAK5 is auto-activated by a central domain that promotes kinase oligomerization. Biochem J. 473:1777–1789
|
139 |
Tyagi N, Bhardwaj A, Singh AP, McClellan S, Carter JE, Singh S (2014) p-21 activated kinase 4 promotes proliferation and survival of pancreatic cancer cells through AKTand ERK-dependent activation of NF-κB pathway. Oncotarget. 5:8778–8789
|
140 |
Udo H, Jin I, Kim JH, Li HL, Youn T, Hawkins RD, Kandel ER, Bailey CH (2005) Serotonin-induced regulation of the actin network for learning-related synaptic growth requires Cdc42, N-WASP, and PAK in Aplysia sensory neurons. Neuron 45:887–901
|
141 |
Walsh KS, Velez JI, Kardel PG, Imas DM, Muenke M, Packer RJ, Castellanos FX, Acosta MT (2013) Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. Dev Med Child Neurol 55:131–138
|
142 |
Wang W, Lim L, Baskaran Y, Manser E, Song J (2013) NMR binding and crystal structure reveal that intrinsically-unstructured regulatory domain auto-inhibits PAK4 by a mechanism different from that of PAK1. Biochem Biophys Res Commun 438:169–174
|
143 |
Wang Y, Zeng C, Li J, Zhou Z, Ju X, Xia S, Li Y, Liu A, Teng H, Zhang K
|
144 |
Willatt L, Cox J, Barber J, Cabanas ED, Collins A, Donnai D, FitzPatrick DR, Maher E, Martin H, Parnau J
|
145 |
Won SY, Park MH, You ST, Choi SW, Kim HK, McLean C, Bae SC, Kim SR, Jin BK, Lee KH
|
146 |
Xia S, Zhou Z, Leung C, Zhu Y, Pan X, Qi J, Morena M, Hill MN, Xie W, Jia Z (2016) p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus. eLife 14:e14653
|
147 |
Yan Z, Kim E, Datta D, Lewis DA, Soderling SH (2016) Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders? J Neurosci 36:11411–11417
|
148 |
Yang N, Higuchi O, Ohashi K, Nagata K, Wada A, Kangawa K, Nishida E, Mizuno K (1998) Cofilin phosphorylation by LIMkinase 1 and its role in Rac-mediated actin reorganization. Nature 393:809–812
|
149 |
Yasui H, Katoh H, Yamaguchi Y, Aoki J, Fujita H, Mori K, Negishi M (2001) Differential responses to nerve growth factor and epidermal growth factor in neurite outgrowth of PC12 cells are determined by Rac1 activation systems. J Biol Chem 276:15298–15305
|
150 |
Zeisel A, Hochgerner H, Lönnerberg P, Johnsson A, Memic F, van der Zwan J, Häring M, Braun E, Borm LE, La Manno G
|
151 |
Zhao L, Ma QL, Calon F, Harris-White ME, Yang F, Lim GP, Morihara T, Ubeda OJ, Ambegaokar S, Hansen JE
|
152 |
Zhong JL, Banerjee MD, Nikolic M (2003) Pak1 and its T212 phosphorylated form accumulate in neurones and epithelial cells of the developing rodent. Dev Dyn 228:121–127
|
/
〈 | 〉 |